Rational design of a ratiometric and targetable fluorescent probe for imaging lysosomal zinc ions

Fluorescent detecting and tracking of zinc ions in living cells has become more and more important because the physiological and pathological functions of zinc are highly associated with the timing and discrete distribution of subcellular zinc ion. For the detection of subcellular zinc concentrations with high spatial and temporal reliability, we report the design, synthesis, properties, and bioimaging evaluation of a fluorescent probe, DQZn4, composed of a quinoline scaffold as the ratiometric signaling unit for Zn(2+) and a dimethylethylamino group as the targeting anchor for lysosomes. In acidic aqueous solution (pH = 5.2), DQZn4 features fluorescence emission maximum at 542 nm due to the resonance charge transfer in 4-alkoxy substituted quinoline. Upon binding Zn(2+), the probe displays significant fluorescent turn-on and ratiometric detection of Zn(2+) with blue shift of 47 nm and remarkable fluorescence ratio changes (R = F(495)/F(542 nm), R/R(0) = 5.1). Confocal imaging experiments establish that DQZn4 is able to localize to lysosomes and respond to lysosomal zinc changes in living cells by using fluorescence ratiometry.